1. Be willing and able to provide written informed consent/assent and HIPPA for the
2. Ages 18-75 years old at time of consent. Female or male patients allowed.
3. ECOG PS of 0-2, KPS >/= 60%.
4. Biopsy proven metastatic triple negative breast cancer (estrogen receptor (<1%),
progesterone receptor (<1%) and no overexpression of HER2, according to American
Society of Clinical Oncology - 2020 College of American Pathologists Guideline
Criteria updated,1,2 as evaluated by local institutions with at least 3 exracranial
lesions of metastatic disease on imaging.
5. PD-L1 positive tumor infiltrate as defined as >/= 1% on IHC using the SP142 Ventana
6. Known gBRCA1/2 status (gBRCA 1/2 negative [e.g. gBRCA wild-type, gBRCA variants of
uncertain significance] are eligible).
7. Patients must have at least 2 extracranial metastatic lesions amenable to high dose
radiotherapy and at least one additional extracranial lesion of measurable disease by
Response Evaluation Criteria in Solid Tumors (RECIST v1.1) that will not be treated
with radiotherapy on this study. Of note, lesions maybe in the same organ but must be
2 cm apart and breast lesions may be treated.
8. Patients must have received at least one and no more than two previous lines of
systemic treatment in the advanced setting with or without immune therapy. Patients
with disease recurrence or progression following neoadjuvant or adjuvant cytotoxic
chemotherapy are not eligible unless they have received at least one line of
chemotherapy with or without immune therapy in the advanced setting. NOTE: Targeted
small molecules (e.g. tyrosine kinase inhibitors), hormonal agents and monoclonal
antibodies that inhibit angiogenesis (e.g. bevacizumab, afilbercept) are not counted
in the number of lines of therapy. Cytotoxic chemotherapy with or without immune
therapy for advanced disease prior to protocol treatment is not permitted within 2
weeks of the protocol treatment. Patients may or may not have received radiotherapy or
neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic
breast cancer, but must be entered on study 2 weeks after their last dose of
radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) for
mTNBC and have sufficient resolution of side effects per physician assessment at time
9. Demonstrate adequate organ function as defined in the table below. All screening labs
to be obtained within 14 days prior to registration.
- Absolute neutrophil count > 1500/mcL
- Platelets >/= 100,000 mm
- Anemia >/= 9.0 g/dL (NOTE: The use of transfusion or other intervention to
achieve Hgb >/= 9.0g/dl is acceptable)
- Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine
clearance ≥ 60 mL/min using Cockcroft-Gault equation for patients with creatinine
levels > 1.5× institutional ULN
- Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN
unless liver metastases are present, in which case they must be ≤ 5×ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless
patient is receiving anticoagulant therapy as long as PT or partial
thromboplastin time (PTT) is within therapeutic range of intended use of
- Activated partial thromboplastin time (aPTT) ≤ 1.5× ULN unless patient is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants
10. Patients must be eligible for radiotherapy, talazoparib, and atezolizumab.
11. Females of childbearing potential must have a negative serum or urine pregnancy test
within 14 days prior to Cycle 1 Day 1. If a urine test is done and it is positive or
cannot be confirmed as negative, a serum pregnancy test will be required. NOTE:
Females are considered of child bearing potential unless they are surgically sterile
(have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
or they are naturally postmenopausal for at least 12 consecutive months.
12. Women of childbearing potential and males must agree to use two effective methods of
contraception or complete abstinence, from the time of signing the informed consent
(females) or first day of study treatment (males), during the course of the study and
for 7 months (females) and for 4 months (males) after the last dose of study drug.
13. Patients must not have active wound healing issues from surgery and sufficient
resolution of surgical side effects, per physician assessment, at time of
14. During participation on this study, no other investigation or commercial agents or
therapy for cancer other than bisphosphonate, rank ligand inhibitors, atezolizumab,
radiotherapy and talazoparib should be administered. NOTE: Patients may have received
bisphosphonates or rank ligand inhibitors prior to and while on enrollment on study.
15. Patients must have the psychological ability and general health that permits
completion of the study requirements and required follow up.
1. gBRCA1/2 pathogenic variant positive
2. Three or more lines of cytotoxic chemotherapy for mTNBC.
3. Previous radiation to the metastases to be treated with radiation on this protocol.
4. Previous PARPi treatment (e.g. talazoparib, niraparib, olazaparib).
5. Progression of breast cancer within the first 3 months of prior immune therapy for
non-metastatic or metastatic breast cancer.
6. Untreated CNS disease (patients with stable CNS disease for at least 28 days and
asymptomatic treated CNS metastases are permitted).
7. History of leptomeningeal disease.
8. History of autoimmune disease that has required systemic treatment (i.e. with use of
disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement
therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
9. Use of systemic glucocorticoid or immunosuppressive medications at time of enrollment.
10. Severe, active co-morbidity such as CHF or unstable angina within last 6 months,
transmural MI within the last 6 months.
11. Acute bacterial or fungal infection requiring IV antibiotics at time of registration.
12. COPD or other respiratory illness requiring hospitalization at time of registration.
13. HIV positive with CD4 count <200 cells/ microliter.
14. Current hormone replacement therapy use.
15. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy. Indolent cancers (such as low
risk prostate or in-situ cancers) that are not being treated, are acceptable.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
18. Receipt of the last dose or treatment of anti-cancer chemotherapy, radiotherapy,
surgery, endocrine therapy, targeted therapy, biologic therapy, or tumor embolization
≤ 2 weeks (4 weeks for any monoclonal Antibody (mAb), 6 weeks for nitrosoureas or
mitomycin C) prior to first dose of study treatment, or has not recovered (i.e., to
≤Grade 1 or Baseline) from clinically significant adverse events (AEs) due to these
previously administered agents.